Dexborneol Amplifies Pregabalin's Analgesic Effect in Mouse Models of Peripheral Nerve Injury and Incisional Pain

被引:2
作者
Shen, Zhen [1 ]
Guo, Yun-Dan [1 ]
Tang, Ming-Ze [1 ]
Zhou, Ping [2 ]
Su, Yu-Xin [3 ]
Shen, Hao-Ran [1 ]
Li, Tao [4 ]
Jiang, Wei [5 ]
Han, Yan-Xing [1 ]
Tie, Cai [6 ]
Cui, Jing-Jing [3 ]
Gao, Tian-Le [1 ]
Jiang, Jian-Dong [1 ,7 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Heart Failure Ctr, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing 100037, Peoples R China
[3] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China
[4] China Acad Chinese Med Sci, Expt Res Ctr, Beijing Key Lab Tradit Chinese Med Basic Res Preve, Beijing 100700, Peoples R China
[5] Zhejiang Zhenyuan Pharmaceut Co Ltd, Shaoxing 312071, Peoples R China
[6] China Univ Min & Technol Beijing, Sch Chem & Environm Engn, State Key Lab Fine Explorat & Intelligent Dev Coal, Beijing 100083, Peoples R China
[7] Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
基金
中国国家自然科学基金;
关键词
chronic pain; combination therapy; neuroinflammation; HMGB1; ATP; Nrf2; NEUROPATHIC PAIN; OXIDATIVE STRESS; DAMAGE; SINOMENINE; MICROGLIA; HEALTH; BLOOD;
D O I
10.3390/antiox13070803
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investigation into the potentiation of pregabalin's analgesic effects by dexborneol, a neuroprotective bicyclic monoterpenoid compound. We performed animal experiments where pain models were induced using two methods: peripheral nerve injury, involving axotomy and ligation of the tibial and common peroneal nerves, and incisional pain through a longitudinal incision in the hind paw, while employing a multifaceted methodology that integrates behavioral pharmacology, molecular biology, neuromorphology, and lipidomics to delve into the mechanisms behind this potentiation. Dexborneol was found to enhance pregabalin's efficacy by promoting its transportation to the central nervous system, disrupting self-amplifying vicious cycles via the reduction of HMGB1 and ATP release, and exerting significant anti-oxidative effects through modulation of central lipid metabolism. This combination therapy not only boosted pregabalin's analgesic property but also notably decreased its side effects. Moreover, this therapeutic cocktail exceeded basic pain relief, effectively reducing neuroinflammation and glial cell activation-key factors contributing to persistent and chronic pain. This study paves the way for more tolerable and effective analgesic options, highlighting the potential of dexborneol as an adjuvant to pregabalin therapy.
引用
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页数:26
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